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https://www.readbyqxmd.com/read/29452091/expression-profiles-and-clinical-value-of-plasma-exosomal-tim-3-and-galectin-9-in-non-small-cell-lung-cancer
#1
Jianwei Gao, Xiangyu Qiu, Xinying Li, Hang Fan, Fang Zhang, Tangfeng Lv, Yong Song
Exosomes are membrane-bound, virus-size vesicles present in circulating blood. Tumor cells are avid producers of exosomes, which are thought to mimic molecular features of parent tumor cells. T-cell Immunoglobulin- and Mucin-domain-containing molecule 3 (Tim-3) is one of the next generation immune checkpoints and can be activated by its ligand Galectin-9, negatively regulating anti-tumor immune response. However, the characteristics of plasma exosomal Tim-3/Galectin-9 (Exo-T/G) in cancer remained unknown. Our study aimed to investigate the expression patterns and clinical value of plasma exosomal total protein (Exo-pro) and Exo-T/G in non-small cell lung caner (NSCLC)...
February 13, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29449897/atezolizumab-feasible-second-line-therapy-for-patients-with-non-small-cell-lung-cancer-a-review-of-efficacy-safety-and-place-in-therapy
#2
REVIEW
Fanny Jean, Pascale Tomasini, Fabrice Barlesi
Advanced non-small cell lung cancer (NSCLC) prognosis is still poor and has recently been reformed by the development of immune checkpoint inhibitors and the approval of anti-PD-1 (programmed cell-death 1) treatments such as nivolumab and pembrolizumab in second line. More recently, atezolizumab (MDPL 3280A), a programmed cell-death-ligand 1 (PD-L1) inhibitor, was also studied in this setting. Here, we report a review of the literature assessing the efficacy, safety, and place of atezolizumab in the second-line treatment of advanced NSCLC...
December 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29448849/development-of-small-molecule-immune-checkpoint-inhibitors-of-pd-1-pd-l1-as-a-new-therapeutic-strategy-for-tumour-immunotherapy
#3
Kui Li, Tian Hongqi
Cancer immunotherapy has been increasingly utilized to treat advanced malignancies. The signalling network of immune checkpoints has attracted considerable attention. Immune checkpoint inhibitors are revolutionizing the treatment options and expectations for patients with cancer. The reported clinical success of targeting the T-cell immune checkpoint receptors PD-1/PD-L1 has demonstrated the importance of immune modulation. Indeed, antibodies binding to PD-1 or PD-L1 have shown remarkable efficacy. However, antibody drugs have many disadvantages, such as their production cost, stability, and immunogenicity, and therefore, small-molecule inhibitors of PD-1 and its ligand PD-L1 are being introduced...
February 16, 2018: Journal of Drug Targeting
https://www.readbyqxmd.com/read/29446615/leveraging-engineering-of-cells-for-drug-delivery
#4
Zhaowei Chen, Quanyin Hu, Zhen Gu
Cell therapy has become a momentum-gathering treatment strategy for a variety of diseases, including cancer, diabetes, hemophilia, and cardiomyopathy. However, clinical applications of conventional cell therapies have often been compromised by rapid decline in viability and function of the transplanted cells due to host recognition and subsequent foreign body rejection. Along this line, cell engineering technologies such as cell encapsulation within microcapsules and immobilization in porous scaffolds have been implemented to address the immunosuppression concerns...
February 15, 2018: Accounts of Chemical Research
https://www.readbyqxmd.com/read/29445158/ackr2-in-hematopoietic-precursors-as-a-checkpoint-of-neutrophil-release-and-anti-metastatic-activity
#5
Matteo Massara, Ornella Bonavita, Benedetta Savino, Nicoletta Caronni, Valeria Mollica Poeta, Marina Sironi, Elisa Setten, Camilla Recordati, Laura Crisafulli, Francesca Ficara, Alberto Mantovani, Massimo Locati, Raffaella Bonecchi
Atypical chemokine receptors (ACKRs) are regulators of leukocyte traffic, inflammation, and immunity. ACKR2 is a scavenger for most inflammatory CC chemokines and is a negative regulator of inflammation. Here we report that ACKR2 is expressed in hematopoietic precursors and downregulated during myeloid differentiation. Genetic inactivation of ACKR2 results in increased levels of inflammatory chemokine receptors and release from the bone marrow of neutrophils with increased anti-metastatic activity. In a model of NeuT-driven primary mammary carcinogenesis ACKR2 deficiency is associated with increased primary tumor growth and protection against metastasis...
February 14, 2018: Nature Communications
https://www.readbyqxmd.com/read/29444918/immunotherapy-a-new-standard-of-care-in-thoracic-malignancies-a-summary-of-the-european-respiratory-society-research-seminar-of-the-thoracic-oncology-assembly
#6
Adrien Costantini, Marta Grynovska, Francesca Lucibello, Jorge Moisés, Franck Pagès, Ming S Tsao, Frances A Shepherd, Hasna Bouchaab, Marina Garassino, Joachim G J V Aerts, Julien Mazières, Michele Mondini, Thierry Berghmans, Anne-Pascale Meert, Jacques Cadranel
In May 2017, the second European Respiratory Society research seminar of the Thoracic Oncology Assembly entitled "Immunotherapy, a new standard of care in thoracic malignancies?" was held in Paris, France. This seminar provided an opportunity to review the basis of antitumour immunity and to explain how immune checkpoint inhibitors (ICIs) work. The main therapeutic trials that have resulted in marketing authorisations for use of ICIs in lung cancer were reported. A particular focus was on the toxicity of these new molecules in relation to their immune-related adverse events...
February 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29443657/il-2-and-beyond-in-cancer-immunotherapy
#7
John M Wrangle, Alicia Patterson, C Bryce Johnson, Daniel J Neitzke, Shikhar Mehrotra, Chadrick E Denlinger, Chrystal M Paulos, Zihai Li, David J Cole, Mark P Rubinstein
The development of the T- and natural killer (NK) cell growth factor IL-2 has been a sentinel force ushering in the era of immunotherapy in cancer. With the advent of clinical grade recombinant IL-2 in the mid-1980s, oncologists could for the first time directly manipulate lymphocyte populations with systemic therapy. By itself, recombinant IL-2 can induce clinical responses in up to 15% of patients with metastatic cancer or renal cell carcinoma. When administered with adoptively transferred tumor-reactive lymphocytes, IL-2 promotes T cell engraftment and response rates of up to 50% in metastatic melanoma patients...
February 2018: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/29442540/management-of-immune-related-adverse-events-in-patients-treated-with-immune-checkpoint-inhibitor-therapy-american-society-of-clinical-oncology-clinical-practice-guideline
#8
Julie R Brahmer, Christina Lacchetti, Bryan J Schneider, Michael B Atkins, Kelly J Brassil, Jeffrey M Caterino, Ian Chau, Marc S Ernstoff, Jennifer M Gardner, Pamela Ginex, Sigrun Hallmeyer, Jennifer Holter Chakrabarty, Natasha B Leighl, Jennifer S Mammen, David F McDermott, Aung Naing, Loretta J Nastoupil, Tanyanika Phillips, Laura D Porter, Igor Puzanov, Cristina A Reichner, Bianca D Santomasso, Carole Seigel, Alexander Spira, Maria E Suarez-Almazor, Yinghong Wang, Jeffrey S Weber, Jedd D Wolchok, John A Thompson
Purpose To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events in patients treated with immune checkpoint inhibitor (ICPi) therapy. Methods A multidisciplinary, multi-organizational panel of experts in medical oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, hematology, emergency medicine, nursing, trialist, and advocacy was convened to develop the clinical practice guideline. Guideline development involved a systematic review of the literature and an informal consensus process...
February 14, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29441454/chemotherapy-and-immunotherapy-for-recurrent-and-metastatic-head-and-neck-cancer-a-systematic-review
#9
REVIEW
Alessandro Guidi, Carla Codecà, Daris Ferrari
Head and neck cancer (HNC) is a fatal malignancy with an overall long-term survival of about 50% for all stages. The diagnosis is not rarely delayed, and the majority of patients present with loco-regionally advanced disease. The rate of second primary tumors after a diagnosis of HNC is about 3-7% per year, the highest rate among solid tumors. Currently, a single-modality or a combination of surgery, radiotherapy and chemotherapy (CHT), is the standard treatment for stage III-IV HNC. For the recurrent/metastatic setting, in the last 40 years great efforts have been made in order to develop a more effective CHT regimen, from the use of methotrexate alone, to the combination of cisplatin (CDDP) and 5-fluorouracile (5FU) or paclitaxel...
February 13, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29441437/immune-checkpoint-blockade-the-new-frontier-in-cancer-treatment
#10
Jeffrey M Clarke, Daniel J George, Stacey Lisi, April K S Salama
Immune checkpoint blockers have revolutionized cancer treatment in recent years. These agents are now approved for the treatment of several malignancies, including melanoma, squamous and non-squamous non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, and head and neck squamous cell carcinoma. Studies have demonstrated the significant impact of immunotherapy versus standard of care on patient outcomes, including durable response and extended survival. The use of immunotherapy-based combination therapy has been shown to further extend duration of response and survival...
February 13, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29441072/fatal-necrotizing-encephalopathy-after-treatment-with-nivolumab-for-squamous-non-small-cell-lung-cancer-case-report-and-review-of-the-literature
#11
Markus Leitinger, Mihael V Varosanec, Slaven Pikija, Romana E Wass, Dave Bandke, Serge Weis, Michael Studnicka, Susanne Grinzinger, Mark R McCoy, Larissa Hauer, Johann Sellner
Immune checkpoint inhibitors are antibodies, which enhance cellular and humoral immune responses and are approved for the treatment of various tumors. Immune-related adverse events (irAE) involving different organs and systems are, however, among the side-effects. Recent reports of severe persistent neurological deficits and even fatal cases underpin the need for better understanding of the exact pathomechanisms of central nervous system (CNS) toxicity. To our knowledge, we report the first biopsy-proven case of fatal necrotizing encephalopathy after treatment with nivolumab...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29440769/epithelial-mesenchymal-transition-emt-signature-is-inversely-associated-with-t-cell-infiltration-in-non-small-cell-lung-cancer-nsclc
#12
Young Kwang Chae, Sangmin Chang, Taeyeong Ko, Jonathan Anker, Sarita Agte, Wade Iams, Wooyoung M Choi, Kyoungmin Lee, Marcelo Cruz
Epithelial-mesenchymal transition (EMT) is able to drive metastasis during progression of multiple cancer types, including non-small cell lung cancer (NSCLC). As resistance to immunotherapy has been associated with EMT and immune exclusion in melanoma, it is important to understand alterations to T-cell infiltration and the tumor microenvironment during EMT in lung adenocarcinoma and squamous cell carcinoma. We conducted an integrated analysis of the immune landscape in NSCLCs through EMT scores derived from a previously established 16 gene signature of canonical EMT markers...
February 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29440175/pan-cancer-molecular-classes-transcending-tumor-lineage-across-32-cancer-types-multiple-data-platforms-and-over-10-000-cases
#13
Chad J Creighton, Fengju Chen, Yiqun Zhang, Don L Gibbons, Benjamin Deneen, David Kwiatkowski, Michael Ittmann
PURPOSE: The Cancer Genome Atlas data resources represent an opportunity to explore commonalities across cancer types involving multiple molecular levels, but tumor lineage and histology can represent a barrier in moving beyond differences related to cancer type. EXPERIMENTAL DESIGN: On the basis of gene expression data, we classified 10224 cancers, representing 32 major types, into ten molecular-based "classes."  Molecular patterns representing tissue or histologic dominant effects were first removed computationally, with the resulting classes representing emergent themes across tumor lineages...
February 9, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29439955/dual-pd1-lag3-immune-checkpoint-blockade-limits-tumor-development-in-a-murine-model-of-chronic-lymphocytic-leukemia
#14
Marina Wierz, Sandrine Pierson, Léa Guyonnet, Elodie Viry, Audrey Lequeux, Anaïs Oudin, Simone P Niclou, Markus Ollert, Guy Berchem, Bassam Janji, Coralie Guérin, Jerome Paggetti, Etienne Moussay
No abstract text is available yet for this article.
February 13, 2018: Blood
https://www.readbyqxmd.com/read/29439857/axitinib-in-combination-with-pembrolizumab-in-patients-with-advanced-renal-cell-cancer-a-non-randomised-open-label-dose-finding-and-dose-expansion-phase-1b-trial
#15
Michael B Atkins, Elizabeth R Plimack, Igor Puzanov, Mayer N Fishman, David F McDermott, Daniel C Cho, Ulka Vaishampayan, Saby George, Thomas E Olencki, Jamal C Tarazi, Brad Rosbrook, Kathrine C Fernandez, Mariajose Lechuga, Toni K Choueiri
BACKGROUND: Previous studies combining PD-1 checkpoint inhibitors with tyrosine kinase inhibitors of the VEGF pathway have been characterised by excess toxicity, precluding further development. We hypothesised that axitinib, a more selective VEGF inhibitor than others previously tested, could be combined safely with pembrolizumab (anti-PD-1) and yield antitumour activity in patients with treatment-naive advanced renal cell carcinoma. METHODS: In this ongoing, open-label, phase 1b study, which was done at ten centres in the USA, we enrolled patients aged 18 years or older who had advanced renal cell carcinoma (predominantly clear cell subtype) with their primary tumour resected, and at least one measureable lesion, Eastern Cooperative Oncology Group performance status 0-1, controlled hypertension, and no previous systemic therapy for renal cell carcinoma...
February 9, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29439670/phase-i-study-of-an-active-immunotherapy-for-asymptomatic-phase-lymphoplasmacytic-lymphoma-with-dna-vaccines-encoding-antigen-chemokine-fusion-study-protocol
#16
Sheeba K Thomas, Soung-Chul Cha, D Lynne Smith, Kun Hwa Kim, Sapna R Parshottam, Sheetal Rao, Michael Popescu, Vincent Y Lee, Sattva S Neelapu, Larry W Kwak
BACKGROUND: There is now a renewed interest in cancer vaccines. Patients responding to immune checkpoint blockade usually bear tumors that are heavily infiltrated by T cells and express a high load of neoantigens, indicating that the immune system is involved in the therapeutic effect of these agents; this finding strongly supports the use of cancer vaccine strategies. Lymphoplasmacytic lymphoma (LPL) is a low grade, incurable disease featuring an abnormal proliferation of Immunoglobulin (Ig)-producing malignant cells...
February 13, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29438695/eradication-of-triple-negative-breast-cancer-cells-by-targeting-glycosylated-pd-l1
#17
Chia-Wei Li, Seung-Oe Lim, Ezra M Chung, Yong-Soo Kim, Andrew H Park, Jun Yao, Jong-Ho Cha, Weiya Xia, Li-Chuan Chan, Taewan Kim, Shih-Shin Chang, Heng-Huan Lee, Chao-Kai Chou, Yen-Liang Liu, Hsin-Chih Yeh, Evan P Perillo, Andrew K Dunn, Chu-Wei Kuo, Kay-Hooi Khoo, Jennifer L Hsu, Yun Wu, Jung-Mao Hsu, Hirohito Yamaguchi, Tzu-Hsuan Huang, Aysegul A Sahin, Gabriel N Hortobagyi, Stephen S Yoo, Mien-Chie Hung
Protein glycosylation provides proteomic diversity in regulating protein localization, stability, and activity; it remains largely unknown whether the sugar moiety contributes to immunosuppression. In the study of immune receptor glycosylation, we showed that EGF induces programmed death ligand 1 (PD-L1) and receptor programmed cell death protein 1 (PD-1) interaction, requiring β-1,3-N-acetylglucosaminyl transferase (B3GNT3) expression in triple-negative breast cancer. Downregulation of B3GNT3 enhances cytotoxic T cell-mediated anti-tumor immunity...
February 12, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29437773/autoimmune-fasciitis-triggered-by-the-anti-programmed-cell-death-1-monoclonal-antibody-nivolumab
#18
Matthew Js Parker, Mark E Roberts, Paul C Lorigan, Daniel G du Plessis, Hector Chinoy
A 43-year-old woman with a history of recently diagnosed metastatic melanoma was commenced on systemic therapy with nivolumab, an anti-programmed cell death-1 monoclonal antibody and one of an increasing group of the so-called 'immune checkpoint inhibitors'. She experienced a dramatic complete response within 6 months of initiation. However, in addition to developing incident autoimmune hypothyroidism, she also developed progressive fatigue, proximal weakness, myalgia and dysphagia. Initial investigations with blood tests, electrophysiology and a muscle biopsy were non-specific or normal...
February 8, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29437767/t-cell-exhaustion-signatures-vary-with-tumor-type-and-are-severe-in-glioblastoma
#19
Karolina Woroniecka, Pakawat Chongsathidkiet, Kristen E Rhodin, Hanna R Kemeny, Cosette A Dechant, Samuel H Farber, Aladine A Elsamadicy, Xiuyu Cui, Shohei Koyama, Christina C Jackson, Landon J Hansen, Tanner M Johanns, Luis Sanchez-Perez, Vidyalakshmi Chandramohan, Yen-Rei A Yu, Darell D Bigner, Amber J Giles, Patrick Healy, Glenn Dranoff, Kent J Weinhold, Gavin P Dunn, Peter E Fecci
PURPOSE: T cell dysfunction is a hallmark of GBM. While anergy and tolerance have been well characterized, T cell exhaustion remains relatively unexplored. Exhaustion, characterized in part by the upregulation of multiple immune checkpoints, is a known contributor to failures amidst immune checkpoint blockade, a strategy that has lacked success thus far in GBM. This study is among the first to examine, and credential as bona fide, exhaustion among T cells infiltrating human and murine GBM...
February 7, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29437040/durable-clinical-benefit-in-metastatic-renal-cell-carcinoma-patients-who-discontinue-pd-1-pd-l1-therapy-for-immune-related-adverse-events-iraes
#20
Dylan J Martini, Lana Hamieh, Rana R McKay, Lauren C Harshman, Raphael Brandao, Craig K Norton, John A Steinharter, Katherine M Krajewski, Xin Gao, Fabio A Schutz, Bradley McGregor, Dominick Bosse, Aly-Khan Lalani, Guillermo de Velasco, M Dror Michaelson, David F McDermott, Toni K Choueiri
The current standard of care for treatment of metastatic renal cell carcinoma (mRCC) patients is PD-1/PD-L1 inhibitors until progression or toxicity. Here we characterize the clinical outcomes for 19 mRCC patients who experienced an initial clinical response (any degree of tumor shrinkage), but after immune-related adverse events (irAEs) discontinued all systemic therapy. Clinical baseline characteristics, outcomes, and survival data were collected. The primary end-point was time to progression from the date of treatment cessation (TTP)...
February 1, 2018: Cancer Immunology Research
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